Entrez ID	Official symbol	Synonyms	Description	Location	Type of protein	External annotation
150684	COMMD1	C2orf5, MURR1	copper metabolism domain containing 1	2p15	protein-coding	Genecard

uniprot_summary

refseq_summary

Proposed scaffold protein that is implicated in diverse physiological processes and whose function may be in part linked to its ability to regulate ubiquitination of specific cellular proteins. Can modulate activity of cullin-RING E3 ubiquitin ligase (CRL) complexes by displacing CAND1; in vitro promotes CRL E3 activity and dissociates CAND1 from CUL1 and CUL2 (PubMed:21778237). Promotes ubiquitination of NF-kappa-B subunit RELA and its subsequent proteasomal degradation. Down-regulates NF-kappa-B activity (PubMed:15799966, PubMed:17183367, PubMed:20048074). Involved in the regulation of membrane expression and ubiquitination of SLC12A2 (PubMed:23515529). Modulates Na(+) transport in epithelial cells by regulation of apical cell surface expression of amiloride-sensitive sodium channel (ENaC) subunits and by promoting their ubiquitination presumably involving NEDD4L. Promotes the localization of SCNN1D to recycling endosomes (PubMed:14645214, PubMed:20237237, PubMed:21741370). Promotes CFTR cell surface expression through regulation of its ubiquitination (PubMed:21483833). Down-regulates SOD1 activity by interfering with its homodimerization (PubMed:20595380). Plays a role in copper ion homeostasis. Involved in copper-dependent ATP7A trafficking between the trans-Golgi network and vesicles in the cell periphery; the function is proposed to depend on its association within the CCC complex and cooperation with the WASH complex on early endosomes (PubMed:25355947). Can bind one copper ion per monomer (PubMed:17309234). May function to facilitate biliary copper excretion within hepatocytes. Binds to phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2) (PubMed:18940794). Involved in the regulation of HIF1A-mediated transcription; competes with ARNT/Hif-1-beta for binding to HIF1A resulting in decreased DNA binding and impaired transcriptional activation by HIF-1 (PubMed:20458141).

COMMD1 is a regulator of copper homeostasis, sodium uptake, and NF-kappa-B (see MIM 164011) signaling (de Bie et al., 2005

Caregory	Description	Value	Value range ( Low - High )	Comment
PLI	The probability of being loss-of-function (LoF) intolerant	0.373	[0, ..., 1]	Genes with high pLI scores (pLI ≥ 0.9) are extremely LoF intolerant, whereby genes with low pLI scores (pLI ≤ 0.1) are LoF tolerant. The score is calculated based on high-quality exome sequence data (ExAC) for 60,706 individuals of diverse ethnicities.
Haploinsufficiency (HI) score rank	Predicted probability of exhibiting haploinsufficiency		[100, ..., 1]	High ranks (e.g. 0-10%) indicate a gene is more likely to exhibit haploinsufficiency, low ranks (e.g. 90-100%) indicate a gene is more likely to NOT exhibit haploinsufficiency (DECIPHER, PMID: 20976243). haploinsufficiency means a single functional copy of a gene is insufficient to maintain its normal function and is extremely intolerant of LoF variation.
Gene brain expressed	Queried gene is expressed in brain tissues	True	[False, True]	The gene expression data are extracted from GTEx v7 and BrainSpan. A gene with the expression value of (log 2 based (TPM+1)) at least 1 TPM/RPKM/FPKM in one or more tissues related to the brain is considered brain-expressed.
Protein brain expressed	Queried protein is expressed in brain tissues	True	[False, True]	The protein expression data are extracted from ProteomicsDB (v2018.09). A protein with the expression value of (log based 10 (iBAQ intensity)) at least 0.5 in one or more tissues related to the brain is considered brain-expressed protein.
Carrying LoF DNMs	Number of loss-of-function DNMs hit the queried gene	0 (Case)	[0, ..., 67] with average of 0.160	Loss of function (LoF) mutations include frameshift indels, nonsense (stop-gained) and splice-site mutations, which can result in the gene product having less or no function and can have deleterious consequences.
		0 (Control)	[0, ..., 6] with average of 0.044
Carrying missense DNMs	Number of missense DNMs hit the queried gene	0 (Case)	[0, ..., 55] with average of 0.846	Missense mutations can result in changes in protein sequences, but are commonly considered to have less deleterious impacts than LoF mutations.
		0 (Control)	[0, ..., 21] with average of 0.300
FMRP binding targets	FMRP inteacting parters	False	[False, True]	FMRP loss of function causes Fragile X syndrome (FXS). The binding targets identified crosslinking immunoprecipitation (HITS-CLIP) in mouse brains (PMID:21784246). Many FMRP targets are among genes implicated in different neuropsychiatric diseases, such as autism, schizophrenia.
Postsynaptic density (PSD)	Protein associates with postsynaptic membranes of excitatory synapses	False	[False, True]	Abnormalities with PSD proteins are linked to various neuropsychiatric diseases including neurodevelopmental disorders.
Human essential genes	-	True	[False, True]	Genes are thought to be critical for human survival.